Affecting 3 to 4% of liveborn infants, birth defects constitute a major health problem, and are now the leading cause of infant mortality in the U.S. Though genetic and chromosomal causes are well described, the majority of birth defects are believed to result from environmental exposures. However, only a small number of agents are known teratogens, and even fewer have been shown to be safe. Every year, new agents are alleged to be teratogenic -- allegations which, because of intense public interest in birth defects and the environment, directly affect the public health and require prompt scientific response. Ongoing case-control surveillance can provide important knowledge about environmental teratogens through the systematic study of birth defects in relation to environmental agents to which pregnant women are exposed, particularly medications and health habits (e.g., smoking). We propose to maintain and expand an existing system of case-control surveillance for birth defects in relation to environmental exposures. Subjects will be drawn from three geographic centers serving a heterogeneous population (the metropolitan areas of Boston, Philadelphia, and Toronto), and will include liveborn and stillborn infants and therapeutic abortuses with major structural malformations, as well as non- malformed subjects, identified through a multi-level ascertainment procedure in each center. Mothers of subjects will be interviewed in their homes by nurses who will administer a detailed and structured questionnaire that elicits information on a wide range of demographic and medical factors, medication use, diet, and health behaviors. A blood sample will also be obtained for testing of biologic markers. This proposal will enable us to: test hypotheses in existing data or through accrual of additional data; generate hypotheses through systematic review of the data; and test and generate hypotheses related to biologically-determined variations in the disposition of drugs and other agents among population subgroups. Should the testing of a new epidemiologic or biologic hypothesis require additional data, the proposed system will facilitate a prompt and efficient response through enhanced accrual of specific defects, modification of the study design and data collection, and modification in the collection of additional biologic markers -- all of which can be accomplished within a few months, rather than years, as is normally required from the time of a study's proposal to the initiation of data collection.